The enkephalinamide compound [D-Met.sup.2, Pro.sup.5 ]-enkephalinamide has been reported to be a potent analgesic agent by Bajusz et al., FEBS Letters 76, 91 (1977).
It has been known in the art that proline can be replaced by thiazolidine-4-carboxylic acid (Thz) in biologically active peptides. See for example Felix et al., Int. J. Pept. Prot. Res. 5, 201 (1973) and Rosamond and Ferger, J. Med. Chem. 19, 873 (1976).
Further it is known that the 2-position in met-enkephalin appears to be sensitive to the nature of the side chain. Hambrook et al., Nature (London) 262, 782 (1976); Pert et al., Science 194, 330 (1976); and Bajusz et al.; Acta Biochim. Biophys. Acad. Sci., Hung. 11, 305 (1976).
Recently Roemer et al., Nature 268, 547 (1977) have reported on several met-enkephalin analogs, the most potent analgesic of the group being D-Ala.sup.2, MePhe.sup.4, Met-O.sup.5 -ol enkephalin which was indicated to be orally active.